{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:35:58Z","timestamp":1768437358905,"version":"3.49.0"},"reference-count":23,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Epinephrine improves return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). These beneficial cardiac effects do not directly translate to better neurologic outcomes, possibly because of epinephrine-induced microvascular effects that produce critical brain ischemia.<\/jats:p><\/jats:sec>Objective<\/jats:title>To examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This retrospective cohort study assessed 14\u202f612 adults from Seattle and King County, Washington, with nontraumatic OHCA between January 1, 2008, and December 31, 2018, and included those who achieved return of spontaneous circulation and were unconscious at hospital admission. Data analysis was performed from April 2021 to May 2022.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Epinephrine dose and TTM during prehospital resuscitation.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Favorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge.<\/jats:p><\/jats:sec>Results<\/jats:title>Of the 14\u202f612 assessed adults, 5253 (median age, 63 years; IQR, 51-74 years; 3460 [65.8%] male) were eligible for the study. The median epinephrine dose was 2.0 mg (IQR, 1.0-3.0 mg); 3052 patients (58.1%) received TTM. In all, 1889 patients (36.0%) survived with CPC 1 to 2, and 2177 (41.4%) survived to discharge. Increasing doses of epinephrine were associated with a decreasing likelihood of CPC 1 to 2 (odds ratio [OR], 0.46; 95% CI 0.42-0.50 for each additional milligram of epinephrine) and survival (OR, 0.47; 95% CI, 0.43-0.51). The dose-dependent epinephrine association was modified by TTM. After adjusting for Utstein covariates, TTM was associated with a relative stepwise improvement in odds of CPC 1 to 2 (interaction OR, 1.36; 95% CI, 1.22-1.51) and survival (interaction OR, 1.37; 95% CI, 1.24-1.51). A significant interaction was also observed when the analysis was stratified according to initial rhythm among shockable OHCA and nonshockable OHCA (shockable interaction OR, 1.20; 95% CI, 1.04-1.39; and nonshockable interaction OR, 1.24, 95% CI, 1.07-1.45).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>This cohort study found an interaction between TTM and epinephrine dose such that the beneficial association of TTM increased with increasing epinephrine dose, suggesting that TTM may attenuate the adverse effects of higher-dose epinephrine.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.26191","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T15:02:12Z","timestamp":1660230132000},"page":"e2226191","source":"Crossref","is-referenced-by-count":12,"title":["Analysis of Epinephrine Dose, Targeted Temperature Management, and Neurologic and Survival Outcomes Among Adults With Out-of-Hospital Cardiac Arrest"],"prefix":"10.1001","volume":"5","author":[{"given":"Betty Y.","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Bulger","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Chocron","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Georges Pompidou European Hospital, Assistance Publique-H\u00f4pitaux de Paris, Paris Sudden Death Expertise Center, University of Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine R.","family":"Counts","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Drucker","sequence":"additional","affiliation":[{"name":"Emergency Medical Services, Division of Public Health\u2013Seattle & King County, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Yin","sequence":"additional","affiliation":[{"name":"Emergency Medical Services, Division of Public Health\u2013Seattle & King County, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megin","family":"Parayil","sequence":"additional","affiliation":[{"name":"Emergency Medical Services, Division of Public Health\u2013Seattle & King County, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Washington, Seattle"},{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nona","family":"Sotoodehenia","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Kudenchuk","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Sayre","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Rea","sequence":"additional","affiliation":[{"name":"Emergency Medical Services, Division of Public Health\u2013Seattle & King County, Seattle, Washington"},{"name":"Division of General Medicine, Department of Medicine, University of Washington, Seattle"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"issue":"8","key":"zoi220740r1","doi-asserted-by":"publisher","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart disease and stroke statistics\u20132021 update: a report from the American Heart Association.","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"issue":"1","key":"zoi220740r2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13054-020-2773-2","article-title":"The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis.","volume":"24","author":"Yan","year":"2020","journal-title":"Crit Care"},{"issue":"24","key":"zoi220740r3","doi-asserted-by":"publisher","first-page":"e881","DOI":"10.1161\/CIR.0000000000000732","article-title":"2019 American Heart Association focused update on advanced cardiovascular life support: use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest: an update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.","volume":"140","author":"Panchal","year":"2019","journal-title":"Circulation"},{"issue":"8","key":"zoi220740r4","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1056\/NEJMoa1806842","article-title":"A randomized trial of epinephrine in out-of-hospital cardiac arrest.","volume":"379","author":"Perkins","year":"2018","journal-title":"N Engl J Med"},{"issue":"12","key":"zoi220740r5","doi-asserted-by":"publisher","first-page":"S454","DOI":"10.1097\/01.CCM.0000247717.81480.B2","article-title":"Microcirculation during cardiac arrest and resuscitation.","volume":"34","author":"Fries","year":"2006","journal-title":"Crit Care Med"},{"issue":"4","key":"zoi220740r6","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1097\/CCM.0b013e31819cedc9","article-title":"Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation.","volume":"37","author":"Ristagno","year":"2009","journal-title":"Crit Care Med"},{"issue":"1","key":"zoi220740r7","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1186\/s13054-020-03297-4","article-title":"Epinephrine\u2019s effects on cerebrovascular and systemic hemodynamics during cardiopulmonary resuscitation.","volume":"24","author":"Mavroudis","year":"2020","journal-title":"Crit Care"},{"key":"zoi220740r8","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.580234","article-title":"Impact of total epinephrine dose on long term neurological outcome for cardiac arrest patients: a cohort study.","volume":"12","author":"Shi","year":"2021","journal-title":"Front Pharmacol"},{"issue":"2","key":"zoi220740r9","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.ccc.2011.10.012","article-title":"Therapeutic hypothermia after cardiac arrest in adults: mechanism of neuroprotection, phases of hypothermia, and methods of cooling.","volume":"28","author":"Weng","year":"2012","journal-title":"Crit Care Clin"},{"issue":"9","key":"zoi220740r10","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004128.pub3","article-title":"Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.","volume":"82","author":"Arrich","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"issue":"2","key":"zoi220740r11","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1177\/175114371401500220","article-title":"Targeted temperature management at 33\u00b0C versus 36\u00b0C after cardiac arrest.","volume":"15","author":"Claxton","year":"2014","journal-title":"J Intensive Care Soc"},{"issue":"24","key":"zoi220740r12","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1056\/NEJMoa1906661","article-title":"Targeted temperature management for cardiac arrest with nonshockable rhythm.","volume":"381","author":"Lascarrou","year":"2019","journal-title":"N Engl J Med"},{"issue":"24","key":"zoi220740r13","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1056\/NEJMoa2100591","article-title":"Hypothermia versus normothermia after out-of-hospital cardiac arrest.","volume":"384","author":"Dankiewicz","year":"2021","journal-title":"N Engl J Med"},{"issue":"7","key":"zoi220740r14","doi-asserted-by":"publisher","first-page":"e208215","DOI":"10.1001\/jamanetworkopen.2020.8215","article-title":"Association of initial illness severity and outcomes after cardiac arrest with targeted temperature management at 36 \u00b0C or 33 \u00b0C.","volume":"3","author":"Callaway","year":"2020","journal-title":"JAMA Netw Open"},{"issue":"8","key":"zoi220740r15","doi-asserted-by":"publisher","first-page":"e741","DOI":"10.1097\/CCM.0000000000005025","article-title":"Outcome related to level of targeted temperature management in postcardiac arrest syndrome of low, moderate, and high severities: a nationwide multicenter prospective registry.","volume":"49","author":"Nishikimi","year":"2021","journal-title":"Crit Care Med"},{"issue":"18","key":"zoi220740r16","doi-asserted-by":"publisher","first-page":"S444","DOI":"10.1161\/CIR.0000000000000261","article-title":"Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.","volume":"132","author":"Link","year":"2015","journal-title":"Circulation"},{"issue":"9596","key":"zoi220740r17","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"370","author":"von Elm","year":"2007","journal-title":"Lancet"},{"issue":"13","key":"zoi220740r18","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1161\/CIR.0000000000000144","article-title":"Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein resuscitation registry templates for out-of-hospital cardiac arrest: a statement for healthcare professionals from a task force of the International Liaison Committee.","volume":"132","author":"Perkins","year":"2015","journal-title":"Circulation"},{"key":"zoi220740r19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.resuscitation.2016.09.006","article-title":"Inter-rater reliability of post-arrest cerebral performance category (CPC) scores.","volume":"109","author":"Grossestreuer","year":"2016","journal-title":"Resuscitation"},{"issue":"12","key":"zoi220740r20","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1097\/CCM.0000000000000547","article-title":"Cerebral performance category at hospital discharge predicts long-term survival of cardiac arrest survivors receiving targeted temperature management.","volume":"42","author":"Hsu","year":"2014","journal-title":"Crit Care Med"},{"issue":"11","key":"zoi220740r22","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1001\/jama.2012.294","article-title":"Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest.","volume":"307","author":"Hagihara","year":"2012","journal-title":"JAMA"},{"key":"zoi220740r23","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.resuscitation.2019.04.018","article-title":"Impact of adrenaline dose and timing on out-of-hospital cardiac arrest survival and neurological outcomes.","volume":"139","author":"Sigal","year":"2019","journal-title":"Resuscitation"},{"key":"zoi220740r21","unstructured":"R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. 2020. Accessed June 30, 2022. https:\/\/www.R-project.org\/"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2795156\/yang_2022_oi_220740_1659531166.69087.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T15:02:14Z","timestamp":1660230134000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2795156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,11]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.26191","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,11]]}}}